Structural insights into heme binding to IL-36α proinflammatory cytokine
Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2019-11, Vol.9 (1), p.16893-14, Article 16893 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 14 |
|---|---|
| container_issue | 1 |
| container_start_page | 16893 |
| container_title | Scientific reports |
| container_volume | 9 |
| creator | Wißbrock, Amelie Goradia, Nishit B. Kumar, Amit Paul George, Ajay Abisheck Kühl, Toni Bellstedt, Peter Ramachandran, Ramadurai Hoffmann, Patrick Galler, Kerstin Popp, Jürgen Neugebauer, Ute Hampel, Kornelia Zimmermann, Bastian Adam, Susanne Wiendl, Maximilian Krönke, Gerhard Hamza, Iqbal Heinemann, Stefan H. Frey, Silke Hueber, Axel J. Ohlenschläger, Oliver Imhof, Diana |
| description | Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins. |
| doi_str_mv | 10.1038/s41598-019-53231-0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6858345</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2314767019</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-f1b509264ff7ea1569919805764ec6575b2cc1f04a93f754cce5cdfe3118b2343</originalsourceid><addsrcrecordid>eNp9kc9OGzEQxi1URCLIC_RQrdRLL1v8f9cXpApRiBSJA_RseR07Md21U9uLlMfiRfpMGEJp4IAvHmt-83lmPgA-I_gdQdKeJoqYaGuIRM0IJqiGB2CKIWU1Jhh_2osnYJbSHSyHYUGROAITgpoSUjgF85scR53HqPrK-eRW65xKkEO1NoOpOueXzq-q8p4vasL_PlSbGJy3vRoGlUPcVnqbw2_nzQk4tKpPZvZyH4NfPy9uz6_qxfXl_PzHota0obm2qGNQYE6tbYxCjAuBRAtZw6nRnDWsw1ojC6kSxDaMam2YXlpDEGo7TCg5Bmc73c3YDWapjc-lebmJblBxK4Ny8m3Gu7VchXvJW9YSyorAtxeBGP6MJmU5uKRN3ytvwphkWWbpkHGOCvr1HXoXxujLeE8UbXhT9l8ovKN0DClFY1-bQVA-mSV3ZskCy2ezJCxFX_bHeC35Z00ByA5IJeVXJv7_-wPZRzZkn_U</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2314767019</pqid></control><display><type>article</type><title>Structural insights into heme binding to IL-36α proinflammatory cytokine</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature OA Free Journals</source><creator>Wißbrock, Amelie ; Goradia, Nishit B. ; Kumar, Amit ; Paul George, Ajay Abisheck ; Kühl, Toni ; Bellstedt, Peter ; Ramachandran, Ramadurai ; Hoffmann, Patrick ; Galler, Kerstin ; Popp, Jürgen ; Neugebauer, Ute ; Hampel, Kornelia ; Zimmermann, Bastian ; Adam, Susanne ; Wiendl, Maximilian ; Krönke, Gerhard ; Hamza, Iqbal ; Heinemann, Stefan H. ; Frey, Silke ; Hueber, Axel J. ; Ohlenschläger, Oliver ; Imhof, Diana</creator><creatorcontrib>Wißbrock, Amelie ; Goradia, Nishit B. ; Kumar, Amit ; Paul George, Ajay Abisheck ; Kühl, Toni ; Bellstedt, Peter ; Ramachandran, Ramadurai ; Hoffmann, Patrick ; Galler, Kerstin ; Popp, Jürgen ; Neugebauer, Ute ; Hampel, Kornelia ; Zimmermann, Bastian ; Adam, Susanne ; Wiendl, Maximilian ; Krönke, Gerhard ; Hamza, Iqbal ; Heinemann, Stefan H. ; Frey, Silke ; Hueber, Axel J. ; Ohlenschläger, Oliver ; Imhof, Diana</creatorcontrib><description>Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-53231-0</identifier><identifier>PMID: 31729440</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/58 ; 101/6 ; 119/118 ; 140/131 ; 140/133 ; 631/45/127/1213 ; 631/535/878/1263 ; 82 ; 82/103 ; 82/16 ; 82/29 ; 82/80 ; 82/83 ; 96 ; 96/21 ; 96/95 ; Arthritis, Rheumatoid - metabolism ; Arthritis, Rheumatoid - pathology ; Autoimmune diseases ; Binding sites ; Cells, Cultured ; Cytokines ; Cytokines - agonists ; Cytokines - chemistry ; Cytokines - metabolism ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Heme ; Heme - metabolism ; Humanities and Social Sciences ; Humans ; Inflammation ; Inflammation Mediators - agonists ; Inflammation Mediators - chemistry ; Inflammation Mediators - metabolism ; Interleukin 1 ; Interleukin-1 - agonists ; Interleukin-1 - chemistry ; Interleukin-1 - metabolism ; Lung diseases ; Models, Molecular ; Molecular Dynamics Simulation ; multidisciplinary ; N-Terminus ; NMR ; Nuclear magnetic resonance ; Protein Binding ; Protein Conformation ; Psoriasis ; Psoriasis - metabolism ; Psoriasis - pathology ; Rheumatoid arthritis ; Science ; Science (multidisciplinary) ; Signal transduction ; Skin diseases ; Structure-Activity Relationship ; Synovial Membrane - metabolism ; Synovial Membrane - pathology ; Synoviocytes</subject><ispartof>Scientific reports, 2019-11, Vol.9 (1), p.16893-14, Article 16893</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-f1b509264ff7ea1569919805764ec6575b2cc1f04a93f754cce5cdfe3118b2343</citedby><cites>FETCH-LOGICAL-c474t-f1b509264ff7ea1569919805764ec6575b2cc1f04a93f754cce5cdfe3118b2343</cites><orcidid>0000-0002-5131-8452 ; 0000-0002-1230-7945 ; 0000-0003-0045-0610 ; 0000-0003-4163-7334 ; 0000-0002-3394-4767</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858345/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858345/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31729440$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wißbrock, Amelie</creatorcontrib><creatorcontrib>Goradia, Nishit B.</creatorcontrib><creatorcontrib>Kumar, Amit</creatorcontrib><creatorcontrib>Paul George, Ajay Abisheck</creatorcontrib><creatorcontrib>Kühl, Toni</creatorcontrib><creatorcontrib>Bellstedt, Peter</creatorcontrib><creatorcontrib>Ramachandran, Ramadurai</creatorcontrib><creatorcontrib>Hoffmann, Patrick</creatorcontrib><creatorcontrib>Galler, Kerstin</creatorcontrib><creatorcontrib>Popp, Jürgen</creatorcontrib><creatorcontrib>Neugebauer, Ute</creatorcontrib><creatorcontrib>Hampel, Kornelia</creatorcontrib><creatorcontrib>Zimmermann, Bastian</creatorcontrib><creatorcontrib>Adam, Susanne</creatorcontrib><creatorcontrib>Wiendl, Maximilian</creatorcontrib><creatorcontrib>Krönke, Gerhard</creatorcontrib><creatorcontrib>Hamza, Iqbal</creatorcontrib><creatorcontrib>Heinemann, Stefan H.</creatorcontrib><creatorcontrib>Frey, Silke</creatorcontrib><creatorcontrib>Hueber, Axel J.</creatorcontrib><creatorcontrib>Ohlenschläger, Oliver</creatorcontrib><creatorcontrib>Imhof, Diana</creatorcontrib><title>Structural insights into heme binding to IL-36α proinflammatory cytokine</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.</description><subject>101/58</subject><subject>101/6</subject><subject>119/118</subject><subject>140/131</subject><subject>140/133</subject><subject>631/45/127/1213</subject><subject>631/535/878/1263</subject><subject>82</subject><subject>82/103</subject><subject>82/16</subject><subject>82/29</subject><subject>82/80</subject><subject>82/83</subject><subject>96</subject><subject>96/21</subject><subject>96/95</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Autoimmune diseases</subject><subject>Binding sites</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Cytokines - agonists</subject><subject>Cytokines - chemistry</subject><subject>Cytokines - metabolism</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - pathology</subject><subject>Heme</subject><subject>Heme - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation Mediators - agonists</subject><subject>Inflammation Mediators - chemistry</subject><subject>Inflammation Mediators - metabolism</subject><subject>Interleukin 1</subject><subject>Interleukin-1 - agonists</subject><subject>Interleukin-1 - chemistry</subject><subject>Interleukin-1 - metabolism</subject><subject>Lung diseases</subject><subject>Models, Molecular</subject><subject>Molecular Dynamics Simulation</subject><subject>multidisciplinary</subject><subject>N-Terminus</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Psoriasis</subject><subject>Psoriasis - metabolism</subject><subject>Psoriasis - pathology</subject><subject>Rheumatoid arthritis</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal transduction</subject><subject>Skin diseases</subject><subject>Structure-Activity Relationship</subject><subject>Synovial Membrane - metabolism</subject><subject>Synovial Membrane - pathology</subject><subject>Synoviocytes</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc9OGzEQxi1URCLIC_RQrdRLL1v8f9cXpApRiBSJA_RseR07Md21U9uLlMfiRfpMGEJp4IAvHmt-83lmPgA-I_gdQdKeJoqYaGuIRM0IJqiGB2CKIWU1Jhh_2osnYJbSHSyHYUGROAITgpoSUjgF85scR53HqPrK-eRW65xKkEO1NoOpOueXzq-q8p4vasL_PlSbGJy3vRoGlUPcVnqbw2_nzQk4tKpPZvZyH4NfPy9uz6_qxfXl_PzHota0obm2qGNQYE6tbYxCjAuBRAtZw6nRnDWsw1ojC6kSxDaMam2YXlpDEGo7TCg5Bmc73c3YDWapjc-lebmJblBxK4Ny8m3Gu7VchXvJW9YSyorAtxeBGP6MJmU5uKRN3ytvwphkWWbpkHGOCvr1HXoXxujLeE8UbXhT9l8ovKN0DClFY1-bQVA-mSV3ZskCy2ezJCxFX_bHeC35Z00ByA5IJeVXJv7_-wPZRzZkn_U</recordid><startdate>20191115</startdate><enddate>20191115</enddate><creator>Wißbrock, Amelie</creator><creator>Goradia, Nishit B.</creator><creator>Kumar, Amit</creator><creator>Paul George, Ajay Abisheck</creator><creator>Kühl, Toni</creator><creator>Bellstedt, Peter</creator><creator>Ramachandran, Ramadurai</creator><creator>Hoffmann, Patrick</creator><creator>Galler, Kerstin</creator><creator>Popp, Jürgen</creator><creator>Neugebauer, Ute</creator><creator>Hampel, Kornelia</creator><creator>Zimmermann, Bastian</creator><creator>Adam, Susanne</creator><creator>Wiendl, Maximilian</creator><creator>Krönke, Gerhard</creator><creator>Hamza, Iqbal</creator><creator>Heinemann, Stefan H.</creator><creator>Frey, Silke</creator><creator>Hueber, Axel J.</creator><creator>Ohlenschläger, Oliver</creator><creator>Imhof, Diana</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5131-8452</orcidid><orcidid>https://orcid.org/0000-0002-1230-7945</orcidid><orcidid>https://orcid.org/0000-0003-0045-0610</orcidid><orcidid>https://orcid.org/0000-0003-4163-7334</orcidid><orcidid>https://orcid.org/0000-0002-3394-4767</orcidid></search><sort><creationdate>20191115</creationdate><title>Structural insights into heme binding to IL-36α proinflammatory cytokine</title><author>Wißbrock, Amelie ; Goradia, Nishit B. ; Kumar, Amit ; Paul George, Ajay Abisheck ; Kühl, Toni ; Bellstedt, Peter ; Ramachandran, Ramadurai ; Hoffmann, Patrick ; Galler, Kerstin ; Popp, Jürgen ; Neugebauer, Ute ; Hampel, Kornelia ; Zimmermann, Bastian ; Adam, Susanne ; Wiendl, Maximilian ; Krönke, Gerhard ; Hamza, Iqbal ; Heinemann, Stefan H. ; Frey, Silke ; Hueber, Axel J. ; Ohlenschläger, Oliver ; Imhof, Diana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-f1b509264ff7ea1569919805764ec6575b2cc1f04a93f754cce5cdfe3118b2343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>101/58</topic><topic>101/6</topic><topic>119/118</topic><topic>140/131</topic><topic>140/133</topic><topic>631/45/127/1213</topic><topic>631/535/878/1263</topic><topic>82</topic><topic>82/103</topic><topic>82/16</topic><topic>82/29</topic><topic>82/80</topic><topic>82/83</topic><topic>96</topic><topic>96/21</topic><topic>96/95</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Arthritis, Rheumatoid - pathology</topic><topic>Autoimmune diseases</topic><topic>Binding sites</topic><topic>Cells, Cultured</topic><topic>Cytokines</topic><topic>Cytokines - agonists</topic><topic>Cytokines - chemistry</topic><topic>Cytokines - metabolism</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - pathology</topic><topic>Heme</topic><topic>Heme - metabolism</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation Mediators - agonists</topic><topic>Inflammation Mediators - chemistry</topic><topic>Inflammation Mediators - metabolism</topic><topic>Interleukin 1</topic><topic>Interleukin-1 - agonists</topic><topic>Interleukin-1 - chemistry</topic><topic>Interleukin-1 - metabolism</topic><topic>Lung diseases</topic><topic>Models, Molecular</topic><topic>Molecular Dynamics Simulation</topic><topic>multidisciplinary</topic><topic>N-Terminus</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Psoriasis</topic><topic>Psoriasis - metabolism</topic><topic>Psoriasis - pathology</topic><topic>Rheumatoid arthritis</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal transduction</topic><topic>Skin diseases</topic><topic>Structure-Activity Relationship</topic><topic>Synovial Membrane - metabolism</topic><topic>Synovial Membrane - pathology</topic><topic>Synoviocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wißbrock, Amelie</creatorcontrib><creatorcontrib>Goradia, Nishit B.</creatorcontrib><creatorcontrib>Kumar, Amit</creatorcontrib><creatorcontrib>Paul George, Ajay Abisheck</creatorcontrib><creatorcontrib>Kühl, Toni</creatorcontrib><creatorcontrib>Bellstedt, Peter</creatorcontrib><creatorcontrib>Ramachandran, Ramadurai</creatorcontrib><creatorcontrib>Hoffmann, Patrick</creatorcontrib><creatorcontrib>Galler, Kerstin</creatorcontrib><creatorcontrib>Popp, Jürgen</creatorcontrib><creatorcontrib>Neugebauer, Ute</creatorcontrib><creatorcontrib>Hampel, Kornelia</creatorcontrib><creatorcontrib>Zimmermann, Bastian</creatorcontrib><creatorcontrib>Adam, Susanne</creatorcontrib><creatorcontrib>Wiendl, Maximilian</creatorcontrib><creatorcontrib>Krönke, Gerhard</creatorcontrib><creatorcontrib>Hamza, Iqbal</creatorcontrib><creatorcontrib>Heinemann, Stefan H.</creatorcontrib><creatorcontrib>Frey, Silke</creatorcontrib><creatorcontrib>Hueber, Axel J.</creatorcontrib><creatorcontrib>Ohlenschläger, Oliver</creatorcontrib><creatorcontrib>Imhof, Diana</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wißbrock, Amelie</au><au>Goradia, Nishit B.</au><au>Kumar, Amit</au><au>Paul George, Ajay Abisheck</au><au>Kühl, Toni</au><au>Bellstedt, Peter</au><au>Ramachandran, Ramadurai</au><au>Hoffmann, Patrick</au><au>Galler, Kerstin</au><au>Popp, Jürgen</au><au>Neugebauer, Ute</au><au>Hampel, Kornelia</au><au>Zimmermann, Bastian</au><au>Adam, Susanne</au><au>Wiendl, Maximilian</au><au>Krönke, Gerhard</au><au>Hamza, Iqbal</au><au>Heinemann, Stefan H.</au><au>Frey, Silke</au><au>Hueber, Axel J.</au><au>Ohlenschläger, Oliver</au><au>Imhof, Diana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural insights into heme binding to IL-36α proinflammatory cytokine</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-11-15</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>16893</spage><epage>14</epage><pages>16893-14</pages><artnum>16893</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Cytokines of the interleukin (IL)-1 family regulate immune and inflammatory responses. The recently discovered IL-36 family members are involved in psoriasis, rheumatoid arthritis, and pulmonary diseases. Here, we show that IL-36α interacts with heme thereby contributing to its regulation. Based on in-depth spectroscopic analyses, we describe two heme-binding sites in IL-36α that associate with heme in a pentacoordinated fashion. Solution NMR analysis reveals structural features of IL-36α and its complex with heme. Structural investigation of a truncated IL-36α supports the notion that the N-terminus is necessary for association with its cognate receptor. Consistent with our structural studies, IL-36-mediated signal transduction was negatively regulated by heme in synovial fibroblast-like synoviocytes from rheumatoid arthritis patients. Taken together, our results provide a structural framework for heme-binding proteins and add IL-1 cytokines to the group of potentially heme-regulated proteins.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31729440</pmid><doi>10.1038/s41598-019-53231-0</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-5131-8452</orcidid><orcidid>https://orcid.org/0000-0002-1230-7945</orcidid><orcidid>https://orcid.org/0000-0003-0045-0610</orcidid><orcidid>https://orcid.org/0000-0003-4163-7334</orcidid><orcidid>https://orcid.org/0000-0002-3394-4767</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2019-11, Vol.9 (1), p.16893-14, Article 16893 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6858345 |
| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry; Springer Nature OA Free Journals |
| subjects | 101/58 101/6 119/118 140/131 140/133 631/45/127/1213 631/535/878/1263 82 82/103 82/16 82/29 82/80 82/83 96 96/21 96/95 Arthritis, Rheumatoid - metabolism Arthritis, Rheumatoid - pathology Autoimmune diseases Binding sites Cells, Cultured Cytokines Cytokines - agonists Cytokines - chemistry Cytokines - metabolism Fibroblasts - metabolism Fibroblasts - pathology Heme Heme - metabolism Humanities and Social Sciences Humans Inflammation Inflammation Mediators - agonists Inflammation Mediators - chemistry Inflammation Mediators - metabolism Interleukin 1 Interleukin-1 - agonists Interleukin-1 - chemistry Interleukin-1 - metabolism Lung diseases Models, Molecular Molecular Dynamics Simulation multidisciplinary N-Terminus NMR Nuclear magnetic resonance Protein Binding Protein Conformation Psoriasis Psoriasis - metabolism Psoriasis - pathology Rheumatoid arthritis Science Science (multidisciplinary) Signal transduction Skin diseases Structure-Activity Relationship Synovial Membrane - metabolism Synovial Membrane - pathology Synoviocytes |
| title | Structural insights into heme binding to IL-36α proinflammatory cytokine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T12%3A40%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structural%20insights%20into%20heme%20binding%20to%20IL-36%CE%B1%20proinflammatory%20cytokine&rft.jtitle=Scientific%20reports&rft.au=Wi%C3%9Fbrock,%20Amelie&rft.date=2019-11-15&rft.volume=9&rft.issue=1&rft.spage=16893&rft.epage=14&rft.pages=16893-14&rft.artnum=16893&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-019-53231-0&rft_dat=%3Cproquest_pubme%3E2314767019%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2314767019&rft_id=info:pmid/31729440&rfr_iscdi=true |